Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 22, Issue 22, Pages 6503-6508Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2014.09.003
Keywords
Phenanthroimidazole derives; c-myc G-quadruplex DNA; pi-pi stacking; Molecular docking
Funding
- Natural Science Foundation of Guangdong Province [S2011040000131]
- Name of the Science and Technology Foundation of Guangdong Province [20070327029]
- Guangdong Province Science and Technology Plan [20771044]
- Guangzhou City Science and Technology Plan [2011J5200017]
- Medical Science and Technology Research Foundation of Guangdong Province [WSTJJ20101231]
- Science and Technology Project of Guangzhou [2012J2200034, 2013J4100072]
- Science Research Program of Guangzhou Municipal Colleges [2012C219]
- Foundation of Guangzhou Medical University [2010C15]
- Department of Science and Technology
- First Affiliated Hospital of Guangdong Pharmaceutical University [GYFYLH201309]
Ask authors/readers for more resources
c-myc G-quadruplex DNA, which plays a central role in tumor progression and resistance, has been extensively investigated as potential target of antitumor drugs. In this paper, a series of phenanthroimidazole derives have been synthesized under irradiation of microwave in yields of 51-80%. The antitumor activity of these compounds against various tumor cells has been evaluated, and the results show that these compounds exhibit great inhibition to MDA-MB-231, MCF-7 and Hela cells, especially 5 inhibit the growth of MDA-MB-231 cells with IC50 about 3.6 mu M. The further studies show that 5 can bind and stabilize c-myc G4 DNA in pi-pi stacking mode, which confirmed by the hypochromise in the electronic spectra of 5 with the increasing of c-myc G4 DNA. When dealt with 5, the strength of CD signal attributed to c-myc G4 DNA is decreased and the FRET melting point of c-myc G4 DNA is increased. Moreover, the molecule docking calculation was conducted to show that 5 suitably stack onto the 50 G-quartet surface, and parallels to the surfaces of the G5 and G-quartet consisting of G7, G11, G16, and G20. As a result, the replication of c-myc oligomers is blocked by 5. In a word, this type of phenanthroimidazole derives can act as potential inhibitor against breast cancer cells by binding and stabilizing c-myc G4 DNA through p-p stacking. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available